Spray-Dried BMS-986165 Dosage Forms for pH-Stable Bioavailability

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing formulations of BMS-986165, a Tyk2 inhibitor, face challenges in providing sufficient bioavailability and stability, especially when co-administered with gastric pH-raising medications and in regions of the gastrointestinal tract with low water availability, and require extended-release formulations.

Innovation Solution

Formulations comprising amorphous BMS-986165 and polymers, such as HPMCAS, in spray-dried dispersions, which provide improved bioavailability and stability, allowing for both immediate and extended release dosage forms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If crystalline BMS-986165 formulations are used, then the formulation is physically stable, but bioavailability is insufficient especially under elevated gastric pH conditions

Engineering Contradiction:

Improvephysical stabilityVSAvoidbioavailability

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent transforms the drug from crystalline to amorphous state, changing its physical form and dissolution properties. The amorphous formulation achieves superior bioavailability (approximately 2-fold increase) compared to crystalline formulations, particularly under elevated gastric pH conditions, while maintaining physical stability through proper formulation design.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent develops composite formulations combining amorphous BMS-986165 with specific excipients and polymers. These composite materials provide both the enhanced bioavailability of the amorphous state and the physical stability needed for storage, resolving the contradiction between stability and bioavailability.

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If amorphous formulations are used, then bioavailability is improved, but physical stability may be compromised

Engineering Contradiction:

ImprovebioavailabilityVSAvoidphysical stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent employs preliminary stabilization techniques during formulation development, including selection of specific excipients and polymers that prevent amorphous-to-crystalline transition during storage. This preliminary action ensures the amorphous formulation maintains both high bioavailability and physical stability over time.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses excipients and polymers as intermediary substances that stabilize the amorphous drug state. These intermediaries prevent molecular reorganization into crystalline forms while maintaining the dissolution advantages of the amorphous state, thus preserving both bioavailability and stability.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Speed

If immediate release formulations are used, then bioavailability is achieved quickly, but extended delivery to colon is insufficient

Engineering Contradiction:

Improvedissolution rateVSAvoiddelivery duration

Core Design Contradiction:

SpeedVSDuration of action of moving object

Solution Approach 1:

The patent segments the release profile into distinct phases: an initial rapid release phase for immediate bioavailability, followed by a sustained release phase for extended colon delivery. This segmentation allows the formulation to satisfy both quick onset and prolonged action requirements.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a dynamic release system that adapts its dissolution rate over time and along the gastrointestinal tract. The formulation provides fast dissolution initially, then transitions to slower, sustained release, enabling both immediate and extended delivery effects.

Inventive Principle:

Principle #15Dynamics

4Duration of action of moving object

If formulations are designed for extended release, then delivery duration is improved, but dissolution rate may be reduced

Engineering Contradiction:

Improvedelivery durationVSAvoiddissolution rate

Core Design Contradiction:

Duration of action of moving objectVSSpeed

Solution Approach 1:

The patent implements a periodic or phased release mechanism where the formulation releases drug in multiple stages: an initial burst release followed by sustained release over an extended period. This periodic action pattern ensures both rapid initial availability and prolonged delivery duration.

Inventive Principle:

Principle #19Periodic action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The amorphous formulations maintain bioavailability and stability, even under elevated gastric pH conditions, and ensure effective drug delivery to the colon, enhancing treatment of inflammatory bowel diseases with improved patient compliance.

Implementation Method 1

Formulations comprising amorphous BMS-986165 and polymers, such as HPMCAS, in spray-dried dispersions

Methodology Applied

Scientific EffectAmorphous solid dispersion:

Implementation Method 2

amorphous BMS-986165 and polymers, such as HPMCAS, in spray-dried dispersions

Methodology Applied

Scientific EffectSpray-drying:

Data Source

PatentUS12521390B2Dosage forms for Tyk2 inhibitors

Publication Date: 2026.01.13 BRISTOL MYERS SQUIBB CO

AI summary

Stable and bioavailable formulations and dosage forms comprising a dispersion (e.g., spray-dried dispersion) of solid amorphous 6-(cyclopropancamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (Formula (I): BMS-986165) in a solid polymer matrix are provided for the treatment of auto-immune and auto-inflammatory diseases such as an inflammatory bowel disease (IBD) and psoriasis.